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Biomedical subjects

R Wheeler

Publications and source records attributed to R Wheeler.

At least 73 records · Page 4Linked to original sources

T lymphocyte subpopulations in idiopathic thrombocytopenic purpura (ITP).

Absolute T cell counts and the relative distributions of antibody-defined helper and cytotoxic/suppressor T lymphocytes are reported in 26 patients with chronic idiopathic thrombocytopenic purpura (ITP). T cell numbers are generally normal in ITP and alterations in relative helper (OKT4 positive) and suppressor (OKT8 positive) T cell numbers show no consistent patterns, although 35% of the cases examined showed inverted distributions. The combined percentages of helper and suppressor T cells consistently exceeded 100% in ITP indicating the presence of increased OKT4+8+ cells in these patients. A cell population, previously defined as SRBC positive and OKT3 negative, was found in the normal group and in ITP patients following splenectomy but was absent in those patients with intact spleens. The role of these changes in the pathogenesis of ITP is discussed.

Adolescent↗

Metabolic acidosis.

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Acid-Base Equilibrium↗

Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.

Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

Carmustine↗

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents↗

Development and evaluation of an inhibitor-releasing matrix for intrauterine devices.

Antifibrinolytic agents when released into the uterine cavity decrease menorrhagia associated with IUD use. Our objective was to develop a matrix that could be incorporated onto an IUD and release anti-fibrinolytic agents. The copolymer ethylene-vinyl acetate (EVA) was selected for detailed study because it has the advantage over other materials in that it can release large molecular weight substances for more than 100 days, and allows incorporation of large amounts of anti-fibrinolytic agents with different molecular weights. Two compounds, tranexamic acid (AMCA, MW=157) and Trasylol (Kunitz pancreatic trypsin inhibitor, (MW=6,500) were incorporated into the EVA matrix and their release rates measured. In vitro studies with AMCA showed that after the initial burst, a constant high release rate was obtained over a prolonged period of time. The in utero release rate of AMCA from the EVA matrix in rabbits was similar to that obtained in vitro. By contrast, the release rate of Trasylol decreased to low levels during incubation in vitro. The release rate of Trasylol in utero however, appeared to be higher than that in vitro.

Animals↗

Flagellar preparations from Pseudomonas aeruginosa: animal protection studies.

Recent reports have suggested that motility is associated with virulence in Pseudomonas aeruginosa. We have confirmed this observation by showing that groups of mice immunized with P. aeruginosa flagellar-antigen preparations display enhanced survival when they are subsequently burned and challenged locally in the burned area with strains of P. aeruginosa. The protection appears to be due to the immobilization of the microorganisms in the burned skin tissue. Liver elongation factor 2 is also protected. The protection afforded by immunization with flagellar-antigen preparations is independent of the somatic antigenic type of the challenging strain but is flagellar-antigen specific. These data suggest that vaccination with flagellar-antigen preparations may provide a viable prophylactic or therapeutic alternative to antibiotic therapy for use in compromised patient population in which P. aeruginosa poses a serious infection threat.

Animals↗

Tarsal coalitions: review of the literature and case report of bilateral dual calcaneonavicular and talocalcaneal coalitions.

Inasmuch as midfoot coalitions do not occur frequently, a preadolescent or early adolescent patient who has persistent complaints of painful flat foot with peroneal or anterior tibial muscle spasm warrants special evaluation. The patient may complain of becoming easily tired or report the onset of pain with increased activity. Clinical examination may reveal local tenderness over the area of the coalition, but this is not a consistent finding. Restricted inversion of the foot with spasm of the peroneals, forefoot abduction or pronation should alert the examining physician that a tarsal coalition may be present. Appropriate roentgenograms examining all of the possibly involved joints should be obtained. These include 45 degrees oblique views of the foot, which usually give a satisfactory view of the calcaneonavicular joint. Coalitions may occur in any of the facets of the talocalcaneal joint and therefore all facets must be evaluated. The anatomic location of the facets can be variable and multiple-angle axial views may be required. We recommend a 45 degrees axial view to visualize the posterior and middle facets, since they are normally parallel in the axial view. If fibrous coalitions are present, the middle facet may be oblique. Tomography is necessary to visualize the anterior facet or to confirm a coalition either in the middle or in the posterior facets.

Adolescent↗

N-Butyl methacrylate and paraffin as an embedding medium for light microscopy.

A method of tissue embedding using n-butyl methacrylate and paraffin is described. Following alcohol dehydration and infiltration with the methacrylate monomer, tissues are embedded in gelatin capsules in a mixture consisting of 3.5 g of paraffin for each 10 ml of methacrylate. Benzoyl peroxide (0.2 g for each 10 ml of monomer) is added as the catalyst and the methacrylate polymerized in a 50 C oven for 18--24 h. Following polymerization the block is trimmed and embedded in paraffin to provide a firm support during sectioning. A water trough attached to the microtome knife is essential to facilitate the handling of sections and ribbons. For serial sections a mixture of equal weights of beeswax and paraffin is used to make the sections adhere to each other. Usual staining procedures can be used since the embedding medium is readily soluble in xylene.

Acrylates↗

Hydroxylation of testosterone at carbons 1, 2, 6, 7, 15 and 16 by the hepatic microsomal fraction from adult female C57BL/6J mice.

The metabolism of a mixture of [4-14C]- and [7 beta-2H]testosterone by the hepatic microsomal fraction from adult femal C57BL/6J mice has been investigated. The following metabolites were identified by their mass spectra and by their retention times on gas chromatography on one or two phases: 1epsilon-, 2beta-, 6alpha-, 6beta-, 7alpha-, 15alpha-, 15beta-, 16alpha- and 16beta-hydroxytestosterone; 6alpha-, 6beta- and 7alpha-hydroxy-4-androstene-3,17-dione; and 4-androstene-3,17-dione. A compound tentatively identified as 6- or 7-oxotestosterone was also isolated. 17beta-Hydroxy-4,6-androstadien-3-one, 17beta-hydroxy-1,4-androstadien-3-one and 4,6-androstadiene-3,17-dione were identified but are considered to arise non-enzymatically from 7alpha-hydroxytestosterone, 1epsilon-hydroxytestosterone and 7alpha-hydroxy-4-androstene-3,17-dione, respectively.

Acclimatization↗

Intraarterial chemotherapy for head and neck cancer, Part 1: Theoretical considerations and drug delivery systems.

The principal objective of regional chemotherapy is tumor cell kill. The rationale for regional delivery is based on the steep dose/response curve exhibited by most antineoplastic agents. Intraarterial (IA) chemotherapy has the potential advantage of increased drug concentration at the tumor site, decreased systemic drug levels, and continuous tumor cell exposure to an antineoplastic agent. Despite these advantages, the use of IA chemotherapy has not been universally accepted. This is in part due to the difficulties associated with establishing and maintaining arterial access. Considerable improvement in the techniques and efficacy of regional therapy for head and neck cancer will be necessary before there is widespread clinical acceptance. These improvements must be based on anatomic and pharmacologic factors that ensure success of regional therapy. In addition, the development of safe, reliable delivery systems will be necessary. Part 1 of this two-part article will review these factors and discuss delivery systems.

Antineoplastic Agents↗

Intraarterial chemotherapy for head and neck cancer, Part 2: Clinical experience.

Despite almost 3 decades of experience, the use of intraarterial (IA) chemotherapy for the treatment of head and neck cancer is not universally accepted. The overall reported response rates are not substantially different from the therapeutic results obtained with systemic therapy. The additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. It is clear that considerable improvement in the techniques and efficacy of IA chemotherapy is necessary. This second and last part of this article considers the past and present clinical experience with IA therapy in the treatment of head and neck cancer and explores future developments.

Antineoplastic Combined Chemotherapy Protocols↗